The mesolimbic and cortical dopamine (DA) system has been a recent focus of the hypothesized relationship between DA and schizophrenia. The DA hypothesis of schizophrenia is currently based on evidence that neuroleptic medications act by blocking central DA receptors and that other drugs altering central DA activity can also affect the symptoms of schizophrenia. The major gap in the DA hypothesis of schizophrenia is lack of direct evidence for DA hyperactivity in unmedicated schizophrenics. It is possible that the basic defect in schizophrenia may lie in a neuronal system controlling DA activity. The action of neuroleptic in schizophrenia would then be analogous to the action of anticholinergics in Parkinson's disease. The anticholinergics decrease the symptoms of Parkinson's disease, even though the primary defect is not cholinergic hyperactivity. By use of combinations of electrical stimulation, single unit recording, microiontophoresis, and histochemical techniques, we propose first to identify and characterize A-10 DA neurons and then elucidate possible influences of specific neuro-regulator systems and mechanisms of action of drugs such as d- and l-amphetamine on these identified A-10 DA cells. The information emerging from these studies should clarify our knowledge of neurochemical basis of amphetamine psychosis and further our understanding of neuroregulator systems which control A-10 DA activity. Ultimately, such knowledge should (1) contribute to the identification of neuronal systems which may be involved in the pathogenesis of schizophrenid, and (2) lead to the development of new neuroleptic agents or neuroleptic supplements which would dampen DA activity by altering afferent neuroregulator systems; neuroleptic supplements might allow lowering dose of neuroleptics with a consequent lessening of the risk of tardive dyskinesia and other side effects induced by neuroleptics.